Biomarkers driving precision medicine in nonfunctioning pituitary neuroendocrine tumors: a systematic review of recent literature

Haydar Ali Tajuddin, Amalina and Isa, Nur Firdaus and Mohd Nasir, Mohd Hamzah (2026) Biomarkers driving precision medicine in nonfunctioning pituitary neuroendocrine tumors: a systematic review of recent literature. The Journal of Clinical Endocrinology and Metabolism, 111 (4). e1195-e1204. ISSN 0021-972X E-ISSN 1945-7197

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Abstract

Nonfunctioning pituitary neuroendocrine tumors (NF-PitNETs) display considerable biological heterogeneity, posing challenges for accurate prognostication and personalized management. This systematic review, conducted in Scopus and Web of Science in accordance with PRISMA 2020, identified 29 primary studies and categorized all molecular findings into 3 core themes: (1) invasion biology and epithelial–mesenchymal transition (EMT); (2) noncoding RNAs and liquid biopsy markers; and (3) multiomics, epigenetic, and prognostic signatures. Within the invasion/EMT theme, gonadotroph tumors consistently demonstrated the strongest EMT-linked activity, including SNAI-mediated transitions, Vimentin upregulation, and β-catenin alterations. Corticotroph tumors showed intermediate EMT involvement, while null-cell tumors exhibited invasion patterns driven mainly by hypoxia-related protease dysregulation rather than EMT. In the noncoding RNA and circulating biomarker theme, several candidates, including exosomal miR-486-5p, miR-151a-5p, and exosomal MMP1, have shown diagnostic or prognostic value, although subtype specificity remains limited. The multiomics and epigenetic theme revealed subtype-dependent molecular programs: gonadotroph tumors were associated with PI3K–AKT pathway enrichment and SF-1 labeling heterogeneity; recurrent lesions showed elevated nuclear pEGFR T693 and MCM7; while DNA methylation mapping identified subtype-relevant loci such as NUP93, LGALS1, and GABRA1. Phosphoproteomic and acetylomic profiling further highlighted alterations in metabolic, kinase-driven, and cell-adhesion pathways linked to invasion and recurrence. Overall, the lineage-aligned synthesis indicates that NF-PitNETs progress through diverse molecular pathways, with each subtype dominated by distinct regulatory networks. Although many biomarkers show promise, most remain exploratory, highlighting the need for harmonized methods and multicenter validation to support precision diagnostics and prognostic modeling

Item Type:	Article (Journal)
Uncontrolled Keywords:	nonfunctioning pituitary neuroendocrine tumors, NF-PitNETs, NFPA, pituitary tumors, biomarkers, precision medicine
Subjects:	R Medicine > RC Internal medicine R Medicine > RC Internal medicine > RC254 Neoplasms. Tumors. Oncology (including Cancer) R Medicine > RC Internal medicine > RC270 Neoplasms. Tumors. Oncology-Cancer and Other Malignant Neoplasms-Therapeutics R Medicine > RC Internal medicine > RC648 Specialties of Internal Medicine-Diseases of The Endocrine Glands. Clinical Endocrinology
Kulliyyahs/Centres/Divisions/Institutes (Can select more than one option. Press CONTROL button):	Kulliyyah of Science > Department of Biotechnology Kulliyyah of Medicine
Depositing User:	Dr Amalina Haydar Ali Tajuddin
Date Deposited:	25 Mar 2026 15:57
Last Modified:	25 Mar 2026 15:59
Queue Number:	2026-03-Q2623
URI:	http://irep.iium.edu.my/id/eprint/128027

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